The polychlorinated ethanes are widely used, economically important compounds which are also well recognized environmental contaminants. Most of these are known to be toxic to certain organ systems, such as liver and kidney, and many are carcinogenic. There is evidence, as with many other chemicals, that some of the adverse health effects are due to certain metabolites formed in vivo. It is also known that most of these compounds undergo extensive hepatic microsomal oxidative or reductive degradation, apparently catalyzed by cytochrome P-450. Relatively little is known, however, about the products of these biotransformations. The focus of this project, therefore, is to continue studies to identify and quantify metabolites of the polychloroethanes using rat hepatic microsomes as the enzyme source. The results will assist in the elucidation of metabolic pathways for these compounds and in attempts to understand relationships between metabolism and toxicity. These data will also assist in predicting metabolic routes of other polyhalogenated alkanes. The specific aims of this project are as follows. (1) Microsomal aerobic and anaerobic metabolites will be identified and quantified. Dynamic head space and chromatographic analyses will be employed for volatile compounds, while other methods including chemical trapping and column or solvent extraction techniques will be employed for nonvolatile-water soluble metabolites. (2) Quantitative data will be compared for metabolite formation and substrate disappearance. Significant discrepancies will indicate covalent binding or unidentified metabolites which will be further investigated using 14C-labeled substrates. (3) The deuterium content of metabolites formed from selectively deuterated substrates will be determined by mass spectrometry. These data will provide information on the mechanisms of these enzymatric conversions. (4) Factors affecting the ratio of cis to trans-1-2-dichloroethylene formation from 1,1,2,2-tetrachloroethane will provide further information on the mechanism of the reductive reactions. (5) Effect of inducing agents and inhibitors on metabolite formation will be determined and the metabolism of polychloroethanes by mouse liver microsomes will be compared to that determined using rat liver.